The overall objective of this proposal is to obtain detailed information concerning the structure of hepatitis B surface antigen (HBsAg) proteins and to determine the relationship between the protein structure and the antigenic structure. The proteins of HBsAg will be isolated and compared by amino acid analysis and a variety of peptide mapping techniques. This should allow the determination of the number of unique proteins and the number of structurally related proteins in HBsAg from different antigenic subtypes (adw,ayw) will be determined. Comparisons of these sequences should allow the identification of the subtype determinant site(s). Specific chemical modifications of HBsAg proteins will be performed and the extent and sites of these modifications correlated with changes in antigenic activity. The location of these chemical modifications within the amino acid sequence should provide additional information concerning the location of the antigenic sites. HBsAg is largely resistant to proteolytic cleavage, however, a chemically modified HBsAg or HBsAg partially unfolded with SDS is less resistant. Enzymatic cleavage of modified HBsAg will be performed with a variety of proteases in an effort toward producing antigenically active peptides. The location of such peptides in these primary stucture world also be determined. These studies should allow the identification of the protein domains which specify the antigenic determinants. This knowledge could permit the chemical synthesis of peptides with the same structure which in turn could be the basis for a synthetic vaccine against hepatitis B virus.